The potential for treatment of diabetes mellitus by transplantation of isolated Islets of Langerhans will be evaluated in streptozotocin induced hyperglycemia-glycosuria in the rat. Initial quantitation of the immune responsiveness of streptozotocin treated rats will be assessed by studying survival of skin grafts, humoral antibody titer to recrystallized ovalbumin and lymphocyte transformation. Subsequently, first-set, second-set and hyperacute rejection of islet allografts will be defined by measuring insulin and glucogon levels in recipients. Efforts to prolong islet allograft function will utilize immunosuppression of recipients, donor pretreatment and in vitro incubation of isolated islets with cytosine arabinoside. Technical problems in increasing the number of islets harvested from human cadaveric pancreata will be explored.